Immunity tutorials Flashcards
How do carcinogens cause cancer at a molecular level?
Carcinogens can result in injury to the cell at genetic level
This can result in mutations or deletion of genes producing abnormal gene products or turning off tumour suppressor genes
Multi step carcinogenesis hypothesis
What is the multi step carcinogenesis hypothesis
Initiation occurs rapidly and is heritable and irreversible. A chemical, physical or biological agent causes permanent damage (i.e. mutation) to
These cells are phenotypically identical to their non-initiated neighbours but genetically different.
Promotion is the event that causes proliferation of
the transformed(initiated) cells. Changes induced by promotors are reversible and promotors do not transform cells that are not initiated.
Progression involves the additional cell divisions that initiated cells undergo (sometimes involving additional mutation) that ultimately result in the development of malignancy
Can you name an important gene in DNA repair?
BRCA1 and BRAC2 associated with breast cancer. Both are DNA repair system genes and are associated with about 25% with familial breast cancer in both men and women
Tp53 is responsible for checking the DNA
of the cell for mutations during cell division
What cell is called “the guardian of the genome”.
The Tp53 is a tumour suppressor gene and is often called “the guardian of the genome”.
To obtain a conclusive diagnosis a biopsy was taken. One of the findings was the downward growth of the malignant epithelium into the muscle layers. This is an important histopathological parameter that must be noted for the assessment of the tissue. What is this process called?
This is called invasion. It is a sign of malignancy. Compare this to benign tumours which are encapsulated and do not show signs of invasion.
Invasion means local spread of the malignancy
Can you explain the role of plasma factors in the clotting process?
Coagulation system – three pathways, intrinsic, extrinsic and common pathways
Leads to production of thrombin which produces fibrin (the clot formation)
Fibrinolytic system – involves activation of plasmin that controls degradation of fibrin clot
The balance between the coagulation and fibrinolytic system is essential – a process known as haemostasis which essentially means to stop the flow of blood.
Too much bleeding vs clotting to death
Explain the central role of macrophages in dictating a chronic inflammatory response?
Recall on the balance between M1 and M2 macrophages in chronic inflammation – different functions, driven by production of different cytokines.
M1 = tissue injury (driving an inflammatory response)
M2 = tissue repair (suppression of inflammatory response)
Can you describe the processes involved in granulation tissue formation
First phase (vascular granulation tissue)
– Mix of proliferating capillaries, fibroblasts, immune cells
– New capillaries are relatively ‘leaky’ allowing cells and fluid into tissue
Second phase (fibrous granulation tissue)
– Over time capillaries regress and immune cells return to blood
- Mature fibroblasts lay down collagen
– Collagen remodelled to an early fibrous scar
What are the main causes of cell injury
Microbial infection
Physical agents (heat, cold, UV radiation)
Irritant and corrosive chemicals
Tissue necrosis
What is the principal mechanism of the hypersensitivity reaction in this allergen scenario and the cells and mediators involved?
Allergens are processed by APCs which are then presented to T helper cells to drive the adaptive response. Plasma B cells will produce copious amounts of IgE that recognise the allergen. Allergens react with IgE antibodies and these complexes bind to receptors on Mast cells and Basophils, and following activation these cells release histamine. This chemical mediator has widespread effects in the body e.g., immune cell recruitment, vasodilation and neurotransmitter (giving you sensation of itching).
Some allergens may also activate the complement cascade which can lead to anaphylactic shock.
What are the 3 complement pathways
- Classical complement pathway – binds via antibody IgG or IgM coating
the bacteria surface - Alternative complement pathway – C3b directly binds to cell surface (cell wall) of a microbial cell.
- Lectin pathway – complement proteins binds to mannose binding lectin
on the cell surface (mannose, a carbohydrate on the surface of microbial cells)
What is the result of complement activation
- Formation of the membrane attack complex (MAC)
- Forms pores on the surface of the bacteria which drives lysis of the cell.
- Anaphylatoxin production by C3/C5a
Explain the processes by which circulating neutrophils are recruited to the site of infection
Cell adhesion molecules control interactions between immune cells (e.g., neutrophils) and endothelial cells;
Three main families
* Selectins (e.g., P and E- selectins)
* Integrins (e.g., LFA-I)
* Immunoglobulin superfamily
Cells will move against a chemokine gradient (e.g., IL-8/CXCL8). These chemokines will be released by cells are site of infection (e.g., epithelial cells and tissue resident immune cells) and due to their endocrine nature will enter circulation and create a gradient (high IL-8 concentration in tissue, low concentration in blood – cells will move towards the higher concentrations of the chemokines)
The cells will undergo a process called diapedesis through interactions between receptors on immune cells and receptors on endothelial cells.
What is the function of neutrophils in clearing threats
MAIN FUNCTION - Phagocytosis
-Also degranulation and production of NETs
Explain how a T cell with a receptor specific for theClostridium tetaniantigen is developed from a pre-thymic T cell in the Thymus
T cells interact with thymic cortical epithelial cells in the thymus
Needs to be a level of “moderate” binding (so that the T cell receptor recognizes the MHC molecule). In positive selection, if no recognition at all cells are destroyed via apoptosis, in negative selection, if the TCR binds too strongly to self-peptide then the T cell is also removed via apoptosis.
T cell receptors are generated through process of somatic recombination.
The VDJ genes are responsible for this – rearrangement of these genes for the variable region of the TCR leads to generation of an antigen binding site that can recognize upwards of 3 x 10^11 antigens.
The constant region of the TCR does not change between receptors
